Johnson & Johnson: CHMP recommends TECVAYLI plus daratumumab for relapsed/refractory multiple myeloma

Regulatory recommendation

The EMA Committee for Medicinal Products for Human Use (CHMP) has recommended approval of an indication extension for teclistamab (TECVAYLI) in combination with daratumumab for adult patients with relapsed or refractory multiple myeloma who have received at least one prior therapy.

Phase 3 efficacy

The CHMP opinion is supported by MajesTEC-3 data. At nearly three years’ follow-up the teclistamab plus daratumumab subcutaneous combination reduced the risk of disease progression or death by 83.4% versus investigator’s choice standard regimens (PFS HR 0.17; 95% CI 0.12–0.23; p<0.0001). More than 90% of patients progression‑free at six months (n=249) remained progression‑free at three years. Overall survival also favoured the combination (OS HR 0.46; 95% CI 0.32–0.65; p<0.0001), with three‑year OS rates of 83.3% versus 65.0% and benefit observed across prespecified subgroups.

Safety

Safety was consistent with the known profiles of the individual agents. All cytokine release syndrome events were Grade 1/2, manageable, and did not lead to discontinuation. Grade 3/4 treatment‑emergent adverse events were comparable between arms (95.1% vs 96.6%), with cytopenias and infections most common. Grade ≥3 infections decreased over time with immunoglobulin supplementation, infection prophylaxis and a switch to monthly dosing; discontinuations for TEAEs were low (4.6% vs 5.5%).

Study design and context

MajesTEC-3 is an ongoing Phase 3 randomised study comparing teclistamab plus daratumumab SC (n=291) versus investigator’s choice daratumumab SC plus dexamethasone with either pomalidomide or bortezomib (n=296) in patients with 1–3 prior lines. The primary endpoint is progression‑free survival; secondary endpoints include depth of response (≥CR), ORR, MRD negativity (10⁻⁵ by NGS), overall survival and patient‑reported symptom worsening (MySIm‑Q).